Protein May Help Lower Infection Deaths in Dialysis

Higher levels of an antimicrobial protein regulated by vitamin D appears to significantly reduce the risk of death from infection in dialysis patients, according to a study in Clinical Infectious Diseases.

The human cathelicidin antimicrobial protein, or hCAP18, is part of the “innate” immune system that helps fight off various bacteria, viruses and fungi. These “antimicrobial peptides” have been researched in recent years because pathogens rarely develop resistance to them, according to the study.

The peptide hCAP18 is of particular interest, researchers said, because it’s the only known antimicrobial peptide of this type in humans. It appears to have the ability to kill a broad range of bacteria, including those that cause tuberculosis and protect against the development of sepsis. This peptide is regulated in the body by vitamin D, and it’s believed that vitamin D therapy may be one mechanism that could boost hCAP18 levels.

The recent study looked at 279 dialysis patients across the United States and found that patients with a high level of hCAP18 were 3.7 times more likely to survive dialysis for a year without a fatal infection. Death from infection is 100 to 300 times higher for dialysis patients than for most people, according to the study.

In addition, the study found that plasma levels of hCAP18 in the dialysis patients were on average about half that of healthy individuals, and that those with the very lowest levels were almost four times as likely to die from infection within a year.

People with severe kidney disease often have unbalanced immune systems, as well as low levels of vitamin D, which plays a key role in the immune response, according to the study. Researchers said administration of active vitamin D analogues to patients undergoing hemodialysis could reduce their mortality rate, but the mechanisms are not understood.

Further studies are needed of the mechanisms of disease prevention with these patients, the researchers said, and whether vitamin D or other therapies can raise hCAP18 levels in these patients and improve their overall survival. This study may also be useful to help physicians identify dialysis patients who are at greatest risk of infection, and be able to address those problems quickly, according to researchers.

Scientists from the Linus Pauling Institute, Cedars-Sinai Medical Center, Harvard Medical School and the University of Copenhagen participated in the study, which was supported by the National Kidney Foundation and the National Institutes of Health.

“The two primary killers of dialysis patients are heart attacks and infections, which often begin around catheters,” said Adrian Gombart, an expert on vitamin D and associate professor in the Linus Pauling Institute at Oregon State University. “If hCAP18 is directly responsible for increases in survival, therapies that increase its levels might be a good adjunct to traditional antibiotics to address this problem.”